The complex genetic and environmental factors affecting human hearing over the lifespan contribute to a large variation in audiometric profiles and suprathreshold measures of auditory function. As a result, determining mechanisms of age-related hearing loss in older adults is challenging because genetic, age, noise history, injury, disease, medication, diet, and other factors can work independently and jointly to alter human auditory function. Although morphologic findings from older humans are limited to postmortem data, experimental procedures with animals of known heredity can disrupt specific cochlear systems, model certain pathologic conditions, and introduce or minimize environmental exposures, while measuring subsequent changes in auditory function. Consistent with results from animal models linking audiometric profiles to specific cochlear pathologies, such as metabolic or sensory loss, audiograms from the Clinical Research Center's human subject database (Core B) were classified into four audiometric phenotypes, which provided a means to characterize the pathophysiology of hearing loss in older humans. Audiometric phenotypes determined using supervised machine learning classifiers were consistent with expected demographic and noise history patterns that segregate with patterns of hearing loss. Project 1 will refine and further validate these phenotyping methods using suprathreshold measures of cochlear and neural function beyond the audiogram that characterize metabolic and sensory presbyacusis, and the additive effects of morphologic and functional neural loss. To meet this goal. Aim 1.1 tests the hypothesis that older adults with metabolic and sensory presbyacusis differ in cochlear nonlinearities and lower frequency suprathreshold auditory function. Aim 1.2 tests the hypothesis that changes in auditory nerve activity result in unique and additive effects in older adults with metabolic and sensory presbyacusis. Thus, Project 1 will assess age related changes in auditory function related to metabolic, sensory, and neural pathologies and link findings to Project 2, focused on central auditory and cortical changes, and to translational Projects 3 and 4, which will determine the genetic and cellular mechanisms of age-related hearing loss using humans and human tissue. With these approaches, morphologic and physiologic changes characterizing metabolic, sensory, and neural presbyacusis provide a framework for assessing and interpreting age-related changes in human auditory function.